“Breakthrough” isn’t a term scientists use often when they talk about a finding. But according to co-organizer Rino Rappuoli of Novartis, attendees of the Keystone meeting on Advancing Vaccines in the Genomics Era, which took place from Oct. 31st until Nov. 4 in Rio de Janeiro, heard talks on not just one, but two breakthroughs, both published in Science on the first day of the meeting.
The perhaps biggest challenge to curing HIV infection is that the virus hides in latently infected, resting memory CD4+ T cells. These cells harbor integrated HIV DNA—the so-called provirus—in their genome, and unless they are activated to produce virus, they are indistinguishable from uninfected resting CD4+ T cells. One strategy to eradicate this reservoir is the so-called “kick and kill” approach: activate the latently infected cells so that they give themselves away by producing virus again, and then kill these virus-producing cells.
Some people infected with HIV can keep the level of virus in their blood in check without any treatment. In part, that’s because these so-called HV controllers carry specific variants of genes for HLA class I proteins, which are involved in the process by which virally infected cells tell specialized immune cells that they should be destroyed. Infected cells use these proteins to present HIV peptides to CD8+ T cells, and it appears that CD8+ T cells kill infected cells more efficiently when they are engaged by the protective variants, which are named B27 and B57. Some researchers believe that another reason for the better control of HIV infection is that when the virus mutates to escape the vigorous CD8+ T-cell attack induced by these variants, it pays a price: It doesn’t replicate very well anymore.
So the AIDS Vaccine conference in Barcelona started up today. And Day One went well, despite the forced absence of some leading scientists, owing to the shutdown of the US government over a budget impasse. Anthony Fauci, Director of the US National Institute of Allergy and Infectious Disease, participated via pre-recorded video, and spoke to journalists live.
HIV always seems to find a way around smartest strategies scientists cook up against it, and keeps coming up with surprises, the more researchers study it. Now cure researchers may well find that their understanding of how HIV hides in latently infected cells—the so-called HIV reservoir—may need to be adjusted, if a recent study is to be believed.